Project Summary Conventional augmentative and alternative communication (AAC) devices for people with severe speech and motor impairments (SSMI) rely on residual motor function, inherently limiting communication throughput. Commercially available AAC solutions require daily caregiver setup, need frequent recalibration often from a technically savvy caregiver, are often unable to be used in dark lighting conditions, and can encumber or fatigue important remaining physical abilities. Furthermore, for people with progressive motor dysfunction due to amyotrophic lateral sclerosis (ALS), even the most well-designed AAC devices will eventually fail as movements become unreliable. For people with brainstem stroke, ALS, and other disorders causing locked-in syndrome (LIS) or SSMI, brain-computer interfaces (BCIs) hold promise as a method of enabling communication that does not rely upon speech or voluntary movement. In prior NIDCD-supported research, our BrainGate research team provided early proofs of principle of a powerful intracortical brain-computer interface (iBCI) that decodes movement intentions directly from brain activity. This technology has allowed people to control a cursor on a computer screen for communication simply by imagining movements of their own arm. The proposed NIDCD U01 clinical research will further the development and testing of a fully implanted iBCI that could provide robust, intuitive control of industry-grade communication apps for people with LIS or SSMI. By leveraging the ongoing pilot clinical trials of the investigational BrainGate system, we aim to (1) improve the robustness and accuracy of neurally actuated point-and click, in part through the translation of neuronal activity from human premotor and motor cortex, (2) expand the number of input dimensions to tablet computers available via neural activity, allowing intended hand gesture commands to control communication apps on touch-screen tablet computers, and (3) rigorously compare the performance of the investigational BrainGate system to trial participants? conventional AAC systems with respect to communication competence, information throughput, user preference and outcomes measures. By incorporating the feedback of six individual participants with paralysis, this feasibility trial will optimize a powerful iBCI for communication and will establish the metrics needed for a subsequent pivotal trial of a fully implanted, always-available iBCI communication system for people with SSMI.